Language：English   Publishing type：Research paper (scientific journal)  

The germline mutation rate is an important parameter that affects the amount of genetic variation and the rate of evolution. However, neither the rate of germline mutations in laboratory mice nor the biological significance of the mutation rate in mammalian populations is clear. Here we studied genome-wide mutation rates and the long-term effects of mutation accumulation on phenotype in more than 20 generations of wild-type C57BL/6 mice and mutator mice, which have high DNA replication error rates. We estimated the base-substitution mutation rate to be 5.4 × 10^-9 (95% confidence interval = 4.6 × 10^-9-6.5 × 10^-9) per nucleotide per generation in C57BL/6 laboratory mice, about half the rate reported in humans. The mutation rate in mutator mice was 17 times that in wild-type mice. Abnormal phenotypes were 4.1-fold more frequent in the mutator lines than in the wild-type lines. After several generations, the mutator mice reproduced at substantially lower rates than the controls, exhibiting low pregnancy rates, lower survival rates, and smaller litter sizes, and many of the breeding lines died out. These results provide fundamental information about mouse genetics and reveal the impact of germline mutation rates on phenotypes in a mammalian population.

DOI： 10.1101/gr.186148.114

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/srep04689

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1046/j.1365-2443.2001.00417.x

Language：English  

Publisher：株式会社医学書院  

DOI： 10.11477/mf.2425201477

CiNii Research

Language：English  

DOI： 10.1038/s41420-022-00961-2

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41420-022-00961-2.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1266/ggs.94.1

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0126710

Language：English   Publishing type：Research paper (scientific journal)  

ΔFosB is a stable transcription factor which accumulates in the nucleus accumbens (NAc), a key part of the brain's reward circuitry, in response to chronic exposure to cocaine or other drugs of abuse. While ΔFosB is known to heterodimerize with a Jun family member to form an active transcription factor complex, there has not to date been an open-ended exploration of other possible binding partners for ΔFosB in the brain. Here, by use of yeast two-hybrid assays, we identify PSMC5 - also known as SUG1, an ATPase-containing subunit of the 19S proteasomal complex - as a novel interacting protein with ΔFosB. We verify such interactions between endogenous ΔFosB and PSMC5 in the NAc and demonstrate that both proteins also form complexes with other chromatin regulatory proteins associated with gene activation. We go on to show that chronic cocaine increases nuclear, but not cytoplasmic, levels of PSMC5 in the NAc and that overexpression of PSMC5 in this brain region promotes the locomotor responses to cocaine. Together, these findings describe a novel mechanism that contributes to the actions of ΔFosB and, for the first time, implicates PSMC5 in cocaine-induced molecular and behavioral plasticity.

DOI： 10.1371/journal.pone.0131263

Language：English  

DOI： 10.7150/ijbs.5750

Language：English   Publishing type：Research paper (scientific journal)  

Changes in the thymic microenvironment lead to radiation-induced thymic lymphomagenesis, but the phenomena are not fully understood. Here we show that radiation-induced chromosomal instability and bystander effects occur in thymocytes and are involved in lymphomagenesis in C57BL/6 mice that have been irradiated four times with 1.8-Gy γ-rays. Reactive oxygen species (ROS) were generated in descendants of irradiated thymocytes during recovery from radiation-induced thymic atrophy. Concomitantly, descendants of irradiated thymocytes manifested DNA lesions as revealed by γ-H2AX foci, chromosomal instability, aneuploidy with trisomy 15 and bystander effects on chromosomal aberration induction in co-cultured ROS-sensitive mutant cells, suggesting that the delayed generation of ROS is a primary cause of these phenomena. Abolishing the bystander effect of post-irradiation thymocytes by superoxide dismutase and catalase supports ROS involvement. Chromosomal instability in thymocytes resulted in the generation of abnormal cell clones bearing trisomy 15 and aberrant karyotypes in the thymus. The emergence of thymic lymphomas from the thymocyte population containing abnormal cell clones indicated that clones with trisomy 15 and altered karyotypes were prelymphoma cells with the potential to develop into thymic lymphomas. The oncogene Notch1 was rearranged after the prelymphoma cells were established. Thus, delayed nontargeted radiation effects drive thymic lymphomagenesis through the induction of characteristic changes in intrathymic immature T cells and the generation of prelymphoma cells.

DOI： 10.1093/jrr/rrs128

Language：English  

DOI： 10.1093/jrr/rrs128

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Mammalian inosine triphosphatase encoded by ITPA gene hydrolyzes ITP and dITP to monophosphates, avoiding their deleterious effects. Itpa^- mice exhibited perinatal lethality, and significantly higher levels of inosine in cellular RNA and deoxyinosine in nuclear DNA were detected in Itpa^- embryos than in wild-type embryos. Therefore, we examined the effects of ITPA deficiency on mouse embryonic fibroblasts (MEFs). Itpa^- primary MEFs lacking ITP-hydrolyzing activity exhibited a prolonged doubling time, increased chromosome abnormalities and accumulation of single-strand breaks in nuclear DNA, compared with primary MEFs prepared from wild-type embryos. However, immortalized Itpa^- MEFs had neither of these phenotypes and had a significantly higher ITP/IDP-hydrolyzing activity than Itpa^- embryos or primary MEFs. Mammalian NUDT16 proteins exhibit strong dIDP/IDP-hydrolyzing activity and similarly low levels of Nudt16 mRNA and protein were detected in primary MEFs derived from both wild-type and Itpa^- embryos. However, immortalized Itpa^- MEFs expressed significantly higher levels of Nudt16 than the wild type. Moreover, introduction of silencing RNAs against Nudt16 into immortalized Itpa^- MEFs reproduced ITPA-deficient phenotypes. We thus conclude that NUDT16 and ITPA play a dual protective role for eliminating dIDP/IDP and dITP/ITP from nucleotide pools in mammals.

DOI： 10.1093/nar/gkp1250

Language：English   Publishing type：Research paper (scientific journal)  

Oxidative base lesions, such as 8-oxoguanine, accumulate in nuclear and mitochondrial DNAs under oxidative stress, resulting in cell death. However, it is not known whether only oxidative lesion accumulated in mitochondrial DNA is involved in such cell death. By introducing human cDNA encoding a nuclear form of 8-oxoG DNA glycosylase (hOGG1-1a) into immortalized mouse embryo fibroblasts lacking Ogg1 gene, we established a cell line which selectively accumulates 8-oxoguanine in mitochondrial DNA under oxidative stress. Selective accumulation of 8-oxoguanine in mitochondrial DNA in this cell line causes degradation of mitochondrial DNA followed by ATP depletion, mitochondrial membrane permeability transition, and Ca(2+) efflux, which in turn activates calpains to execute cell death. Knockdown of MUTYH which excises adenine opposite 8-oxoG in DNA prevents degradation of mitochondrial DNA and activation of calpain, thus suppressing the cell death induced by menadione.

DOI： 10.1007/978-1-59745-521-3_16

Language：English   Publishing type：Research paper (scientific journal)  

8-Oxoguanine (8-oxoG), an oxidized form of guanine, is one of the major mutagenic lesions generated under oxidative stress. Oxidative damage in mitochondrial DNA has been implicated as a causative factor for a wide variety of degenerative diseases as well as for cancer during aging. We established a quantitative method for in situ detection of 8-oxoG in mitochondrial DNA in a single-cell level using a monoclonal antibody. Specific detection of 8-oxoG in mitochondrial DNA was confirmed by pre-treatment of samples with DNase I or MutM, the latter excising 8-oxoG opposite C in DNA. We then analyzed 8-oxoG dynamics in mitochondrial DNA of the wild-type and 8-oxoG DNA glycosylase (OGG1)-deficient mouse cells after exposure to hydrogen peroxide. Intensities for the 8-oxoG immunoreactivity in mitochondrial DNA were increased immediately after the exposure to hydrogen peroxide in both types of cells. The increased intensities returned to basal levels within a few hours only in wild-type cells, but not in OGG1-deficient cells which exhibited the increased intensities even 24 h after the exposure. These results indicate that OGG1 is a major enzyme for excision repair of 8-oxoG in mitochondrial DNA in mouse cells, and that our method described here is appropriate to study 8-oxoG dynamics in mitochondrial DNA.

DOI： 10.1007/978-1-59745-521-3_13

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

It has been shown that molecular hydrogen (H₂) acts as a therapeutic antioxidant and suppresses brain injury by buffering the effects of oxidative stress. Chronic oxidative stress causes neurodegenerative diseases such as Parkinson's disease (PD). Here, we show that drinking H₂-containing water significantly reduced the loss of dopaminergic neurons in PD model mice using both acute and chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The concentration-dependency of H₂ showed that H₂ as low as 0.08 ppm had almost the same effect as saturated H₂ water (1.5 ppm). MPTP-induced accumulation of cellular 8-oxoguanine (8-oxoG), a marker of DNA damage, and 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation were significantly decreased in the nigro-striatal dopaminergic pathway in mice drinking H₂-containing water, whereas production of superoxide (O₂·^-) detected by intravascular injection of dihydroethidium (DHE) was not reduced significantly. Our results indicated that low concentration of H₂ in drinking water can reduce oxidative stress in the brain. Thus, drinking H₂-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration.

DOI： 10.1371/journal.pone.0007247

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

A second class II AP endonuclease, APEX2, possesses strong 3′-5′ exonuclease and 3′-phosphodiesterase activities but only very weak AP-endonuclease activity. APEX2 associates with proliferating cell nuclear antigen (PCNA), and the progression of S phase of the cell cycle is accompanied by its expression. APEX2-null mice exhibit severe dyslymphopoiesis in thymus as well as moderate dyshematopoiesis and growth retardation. Comparative gene expression profiling of wild-type and APEX2-null mice using an oligonucleotide microarray revealed that APEX2-null thymus has significantly altered gene expression profiles, reflecting its altered populations of thymocytes. Beyond these altered populations, APEX2-null thymus exhibits significant alterations in expression of genes involved in DNA replication, recombination and repair, including Apex1, Exo1 and Fen1 as well as master genes for the DNA damage response, such as E2f1, Chek1, and proapoptotic genes. We therefore examined the extent of DNA strand breakage, and found that both of single-strand breaks detected as comets and double-strand breaks detected as γH2AX foci were significantly higher in frequency in most APEX2-null thymocytes compared to wild-type thymocytes. This higher frequency of DNA breaks was accompanied by increased expression of PCNA and increased phosphorylation of p53 at Ser23 and to a lesser extent, at Ser18. The present study clearly demonstrates that APEX2-null lymphocytes have a higher frequency of DNA breaks, indicating that APEX2 may play an important role(s) during their generation and/or repair.

DOI： 10.1016/j.dnarep.2008.05.003

Language：English   Publishing type：Research paper (scientific journal)  

Human MutT homolog (hMTH1) hydrolyzes oxidized purine nucleoside triphosphates to monophosphates, thereby avoiding incorporation of such oxidized purines into DNA or RNA. We examined whether hMTH1 prevents cellular dysfunction induced by sodium nitroprusside, a spontaneous NO donor. Exposure to sodium nitroprusside caused an 8-oxoguanine (8-oxoG) buildup in DNA of proliferating MTH1-null cells which underwent mitochondrial degeneration and subsequently died. Quiescent MTH1-null cells also died with 8-oxoG buildup but only when the buildup affected mitochondrial and not nuclear DNA. In both proliferative and quiescent conditions, the accumulation of 8-oxoG in DNA and cell death was effectively prevented by hMTH1. Knockdown of MUTYH in quiescent MTH1-null cells significantly prevented the cell death, suggesting that 8-oxoG incorporated into mitochondrial DNA is a main cause of this form of cell death. To verify this possibility, an artificially modified hMTH1, namely mTP-EGFP-hMTH1, which localizes exclusively in mitochondria, was expressed in MTH1-null cells. mTP-EGFP-hMTH1 selectively prevented buildup of 8-oxoG in mitochondrial but not nuclear DNA after exposure of proliferating cells to sodium nitroprusside, and also efficiently prevented cell death. We thus concluded that exposure of cells to sodium nitroprusside causes oxidation of mitochondrial deoxynucleotide pools, and that buildup of oxidized bases in mitochondrial DNA initiates cell death.

DOI： 10.1016/j.dnarep.2007.11.007

Language：English   Publishing type：Research paper (scientific journal)  

Oxidative base lesions, such as 8-oxoguanine (8-oxoG), accumulate in nuclear and mitochondrial DNAs under oxidative stress, resulting in cell death. However, it is not known which form of DNA is involved, whether nuclear or mitochondrial, nor is it known how the death order is executed. We established cells which selectively accumulate 8-oxoG in either type of DNA by expression of a nuclear or mitochondrial form of human 8-oxoG DNA glycosylase in OGG1-null mouse cells. The accumulation of 8-oxoG in nuclear DNA caused poly-ADP-ribose polymerase (PARP)-dependent nuclear translocation of apoptosis-inducing factor, whereas that in mitochondrial DNA caused mitochondrial dysfunction and Ca ²⁺ release, thereby activating calpain. Both cell deaths were triggered by single-strand breaks (SSBs) that had accumulated in the respective DNAs, and were suppressed by knockdown of adenine DNA glycosylase encoded by MutY homolog, thus indicating that excision of adenine opposite 8-oxoG lead to the accumulation of SSBs in each type of DNA. SSBs in nuclear DNA activated PARP, whereas those in mitochondrial DNA caused their depletion, thereby initiating the two distinct pathways of cell death.

DOI： 10.1038/sj.emboj.7601975

Language：English   Publishing type：Research paper (scientific journal)  

8-Oxoguanine (8-oxoG), a major spontaneous form of oxidative DNA damage, is considered to be a natural cause of genomic diversity in organisms because of its mutagenic potential. The steady-state level of 8-oxoG in the nuclear genome of a human cell has been estimated to be several residues per 10⁶ guanines. In the present study, to clarify the genome-wide distribution of 8-oxoG in the steady state, we performed fluorescence in situ detection of 8-oxoG on human metaphase chromosomes using a monoclonal antibody. Multiple dot-like signals were observed on each metaphase chromosome. We then mapped the position of the signal at megabase resolution referring to the cytogenetically identified chromosomal band, and demonstrated that 8-oxoG is unevenly distributed in the normal human genome and that the distribution pattern is conserved among different individuals. Moreover, we found that regions with a high frequency of recombination and single nucleotide polymorphisms (SNPs) are preferentially located within chromosomal regions with a high density of 8-oxoG. Our findings suggest that 8-oxoG is one of the main causes of frequent recombinations and SNPs in the human genome, which largely contribute to the genomic diversity in human beings.

DOI： 10.1101/gr.4769606

Language：English   Publishing type：Research paper (scientific journal)  

We previously reported that 8-oxoguanine (8-oxoG) accumulates in the cytoplasm of dopamine neurons in the substantia nigra of patients with Parkinson's disease and the expression of MTH1 carrying an oxidized purine nucleoside triphosphatase activity increases in these neurons, thus suggesting that oxidative damage in nucleic acids is involved in dopamine neuron loss. In the present study, we found that levels of 8-oxoG in cellular DNA and RNA increased in the mouse nigrostriatal system during the tyrosine hydroxylase (TH)-positive dopamine neuron loss induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MTH1-null mice exhibited a greater accumulation of 8-oxoG in mitochondrial DNA accompanied by a more significant decrease in TH and dopamine transporter immunoreactivities in the striatum after MPTP administration, than in wild-type mice. We thus demonstrated that MTH1 protects the dopamine neurons from oxidative damage in the nucleic acids, especially in the mitochondrial DNA of striatal nerve terminals of dopamine neurons.

DOI： 10.1038/sj.cdd.4401788

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/sj.cdd.4401648

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1182/blood-2004-04-1476

Language：English   Publishing type：Research paper (scientific journal)  

In mammalian cells, more than one genome in a single cell has to be maintained throughout the entire life of the cell, namely, one in the nucleus and the other in the mitochondria. The genomes and their precursor nucleotides are highly exposed to reactive oxygen species, which are inevitably generated as a result of the respiratory function in mitochondria. To counteract such oxidative damage in nucleic acids, cells are equipped with several defense mechanisms. Modified nucleotides in the nucleotide pools are hydrolyzed, thus avoiding their incorporation into DNA or RNA. Damaged bases in DNA with relatively small chemical alterations are mainly repaired by the base excision repair (BER) system, which is initiated by the excision of damaged bases by specific DNA glycosylases. MTH1 protein hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP, 8-oxo-dATP, and 2-hydroxy (OH)-dATP to the monophosphates, and MTH1 are located in the cytoplasm, mitochondria, and nucleus. We observed an increased susceptibility to spontaneous carcinogenesis in Mth1-deficient mice and an alteration of MTH1 expression along with the accumulation of 8-oxo-dG in patients with various neurodegenerative diseases. Enzymes for the BER pathway, namely, 8-oxoG DNA glycosylase (OGG1), 2-OH-A/adenine DNA glycosylase (MUTYH), and AP endonuclease (APEX2) are also located both in the mitochondria and in the nuclei, and the expression of mitochondrial OGG1 is altered in patients with various neurodegenerative diseases. We also observed increased susceptibilities to spontaneous cardiogenesis in OGG1 and MUTYH-deficient mice. The increased occurrence of lung tumor in OGG1-deficient mice was completely abolished by the concomitant disruption of the Mth1 gene.

DOI： 10.1196/annals.1293.011

Language：English   Publishing type：Research paper (scientific journal)  

MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-2′-deoxyguanosine 5′-triphosphate (8-oxo-dGTP) and 2-hydroxy-2′-deoxyadenosine 5′-triphosphate (2-OH-dATP) and thus protects cells from damage caused by their misincorporation into DNA. In the present study, we established MTH1-null mouse embryo fibroblasts that were highly susceptible to cell dysfunction and death caused by exposure to H ₂O₂, with morphological features of pyknosis and electron-dense deposits accumulated in mitochondria. The cell death observed was independent of both poly(ADP-ribose) polymerase and caspases. A high performance liquid chromatography tandem mass spectrometry analysis and immunofluorescence microscopy revealed a continuous accumulation of 8-oxo-guanine both in nuclear and mitochondrial DNA after exposure to H ₂O₂. All of the H₂O₂-induced alterations observed in MTH1-null mouse embryo fibroblasts were effectively suppressed by the expression of wild type human MTH1 (hMTH1), whereas they were only partially suppressed by the expression of mutant hMTH1 defective in either 8-oxo-dGTPase or 2-OH-dATPase activity. Human MTH1 thus protects cells from H₂O₂-induced cell dysfunction and death by hydrolyzing oxidized purine nucleotides including 8-oxo-dGTP and 2-OH-dATP, and these alterations may be partly attributed to a mitochondrial dysfunction.

DOI： 10.1074/jbc.M306201200

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1074/jbc.C300047200

Language：English   Publishing type：Research paper (scientific journal)  

The polypurine/polypyrimidine (PuPy) tracts present in the human genome are known to be scattered among and within chromosomes. In PuPy tract sequences, triplex formation occurs readily under physiological conditions, leaving single-stranded DNAs capable of hybridization with complementary single-stranded DNAs and RNAs. The formation of single-strands and transmolecular triplexes is thought to enable sequences spaced distantly along the genome to associate with each other and organize nuclear DNA into ordered configurations. Triplex-forming DNAs in the human interphase nucleus were analyzed by combining fluorescence in situ "non-denaturing" hybridization employing PuPy tract probes and immunodetection by antitriplex antibodies. The non-denaturing hybridization technique, which has been used to detect RNA, may detect single-stranded DNAs in non-denatured nuclei, if present. Probes such as (GA/TC)_n and (GAA/TTC)_n sequences gave sequence-specific signals that overlapped with or were closely associated with triplexes immunolocalized by using known antitriplex antibodies. Pretreatment of nuclei with antitriplex antibodies blocked probe signal formation. Signal formation was resistant to pretreatment of nuclei with RNases but sensitive to single strand-specific nucleases. Triplexes visualized differentially with distinct PuPy tract probes were associated spatially with centromeric sequences in the interphase nucleus in a sequence-specific manner.

DOI： 10.1007/s00412-002-0198-0

Language：English   Publishing type：Research paper (scientific journal)  

The position-independent expression of transgenes in target cells is an essential subject for determining effective gene therapies. The chicken β- globin insulator blocks the effects of regulatory sequences on transcriptional units at differential domains. We prepared a recombinant adeno-associated virus (rAAV) containing various combinations of the DNase I- hypersensitive site 2 (HS2), 3 (HS3), and 4 (HS4) core elements from the human β-globin locus control region (LCR), the human β-globin gene, and the herpes virus thymidine kinase promoter driven neomycin-resistant gene (neo(R)) (rHS432, rHS43, rHS42, rHS32, and rHS2), and also rAAV containing two copies of the 250-bp core sequence of the chicken β-globin insulator on both sides of the rHS2 (rIns/HS2/2Ins). After isolating neomycin-resistant mouse erythroleukemia (MEL) cells infected with each rAAV, we analyzed the rAAV genome by Southern blots and polymerase chain reaction (PCR), using primers specific for HS core elements and the human β-globin gene. All clones contained a single copy of the rAAV genome in the chromosome, however, some of them had a rearranged proviral genome. In five clones with a single unrearranged rAAV genome for each rAAV construct, we assayed the expression of the human b-globin gene relative to the endogenous mouse β(maj)-globin gene, using quantitative reverse transcriptase (RT)-PCR. In clones infected with rHS432, the expression level of the human β-globin gene ranged from 51.6% to 765.6% of that in the mouse β(maj)globin gene. Likewise, in rHS43, the expression level ranged from 36.7% to 259.0%; in rHS42, from 47.8% to 207.0%; in rHS32, from 47.9% to 105.4%; and in rHS2, from 6.1% to 172.1%, indicating a high variability of expression level in clones infected with recombinant virus lacking the insulator. In contrast, in clones infected with rIns/HS2/Ins, the range of expression of the human β-globin gene ranged from 52.8% to 58.3% of that in the mouse β(maj)globin gene. These results indicate that the insulator functioned dramatically to reduce the variability of transgene expression due to the position effect. This insulator-rAAV vector system holds promise to provide a constant level of transgene expression for gene therapy, regardless of the insertion sites on the chromosome.

DOI： 10.1007/s100380050133

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Event date： 2023.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：熊本   Country：Japan  

Event date： 2023.8 - 2023.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：Melbourne   Country：Austria  

Event date： 2023.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：Melbourne   Country：Australia  

Event date： 2022.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：幕張   Country：Japan  

Event date： 2022.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：幕張   Country：Japan  

Event date： 2022.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：広島   Country：Japan  

Event date： 2022.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：広島   Country：Japan  

Event date： 2022.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：大阪   Country：Japan  

Event date： 2022.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪   Country：Japan  

Event date： 2022.8 - 2022.9

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Ottawa, Canada   Country：Canada  

Event date： 2021.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横須賀   Country：Japan  

Event date： 2021.11

Language：Japanese  

Venue：横須賀   Country：Japan  

Event date： 2021.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横須賀   Country：Japan  

Event date： 2021.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2020.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：熊本   Country：Japan  

Event date： 2019.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Event date： 2019.11

Language：English  

Venue：東京   Country：Japan  

Event date： 2019.11

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：京都   Country：Japan  

Event date： 2019.8

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：Manchester   Country：United Kingdom  

Event date： 2018.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜   Country：Japan  

Event date： 2017.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2017.11

Language：Japanese  

Venue：東京   Country：Japan  

Event date： 2017.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：千葉   Country：Japan  

がん組織に蓄積された体細胞突然変異は、がんの細胞系譜史を推測する手がかりとなる。発がんに至る過程またはがんの増殖過程で生じたゲノム損傷やDNA修復機構の変動などに起因して特徴的な変異スペクトルを示すと考えられる。また近年、がん組織中で検出される体細胞変異の半数以上は、発がんに至る以前に生じていることが示され、正常組織における突然変異頻度の上昇と生涯発がんリスクが関連していることが予測される。
　我々はこれまでに、各種DNA損傷とその修復機構に注目し、突然変異と発がんの関連を明らかにするため、マウスを用いた個体レベルでの研究を展開しており、ヒトのがんゲノムデータからの知見の実験的検証につながる結果を得ている。本シンポジウムでは、ヒト遺伝性大腸がんモデルマウスを用いての酸化ストレス誘発消化管発がんの研究プロジェクトの結果を中心に紹介する。グアニンの酸化体である8-オキソグアニンはDNA複製の過程でアデニンと誤対合を形成しG>T塩基置換型変異を引き起こす。MUTYHは塩基除去修復酵素で、この変異の発生を抑制している。Mutyh遺伝子を欠損させたマウスでは、酸化ストレス負荷の度合いに伴い、発がん前の正常組織での体細胞突然変異頻度の上昇および腫瘍発生頻度の上昇を認めた。また、発生した腫瘍のエクソーム解析からは、DNA修復機構の不全であることに起因したG>T変異を主体とする特徴的変異パターンを認め、これはヒトのMUTYH関連大腸腺腫症（MAP）の腫瘍で認められた変異シグネチャーと酷似していた。これらの結果は、MAP患者では酸化ストレスが直接的な発がん要因であり、早期から酸化ストレスを軽減することにより生涯腫瘍発生頻度をコントロールできる可能性を示唆している。発がんの過程をゲノムレベルの変化として捉えることで、がんの発生や増殖に関連する因子を推測し、予防や治療に有効な情報が得られる可能性がある。

Event date： 2017.9

Language：English   Presentation type：Oral presentation (general)  

Venue：横浜   Country：Japan  

Colorectal cancer (CRC) is one of the most common cancers, and oxidative stress is predicted to play an important role in the pathogenesis of CRC. MUTYH is an adenine DNA glycosylase that suppresses oxidative stress-induced mutagenesis by removing adenine mispaired with 8-oxoguanine (8-oxoG), a major oxidative DNA damage. Biallelic mutations in MUTYH gene cause an inherited predisposition to CRC, known as MUTYH-associated polyposis (MAP). Since oxidative stress-induced mutations would be relevant to driving force for tumorigenesis, we studied the property of somatic mutations in the intestines of Mutyh-deficient mice. We found a clear correlation among the levels of oxidative stress, the induced mutation frequency in pre-cancerous tissues, and the tumor incidence. Moreover, whole-exome analysis of tumors developed in the mice revealed a specific mutational pattern; predominant G:C > T:A mutations in the specific sequence contexts, which is resulted from unrepaired 8-oxoG:A mispairings. This pattern was also observed in the somatic mutations detected in the tumors from MAP patients. Thus, avoiding excess oxidative stress can be helpful to reduce a lifetime risk of CRC for MAP patients.

Event date： 2017.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：岡山大学   Country：Japan  

Event date： 2017.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：岡山大学   Country：Japan  

Event date： 2016.11 - 2016.12

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2016.11 - 2016.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2016.11 - 2016.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

新たに生殖細胞に生じる変異（de novo germline mutation: dGM）は多様性を創出し、ゲノム進化の原動力となるが、一方で遺伝病や先天異常の原因にもなる。哺乳類におけるdGMの発生と抑制の機構の解明は、進化学的にも、ヒトの病気の起源を理解する上でも重要である。次世代シーケンス技術の進歩に伴い、ヒトの親子サンプルを用いたdGMの解析が盛んに行われた結果、その頻度やパターンは年齢、性別、ゲノム領域などによって異なることがシーケンスレベルで明らかとなった。これらの事実は、突然変異率には、DNA複製の正確性だけでなく、種々の因子が関与している事を示している。我々は、通常の生活環境下で恒常的に発生するDNA損傷と、それらに起因して誘発される自然突然変異がdGM頻度に影響しているのではないかと考えており、現在はDNA修復機構を欠損したマウス家系を用いてdGMの検出と解析を行っている。これまでに酸化DNA修復機構とミスマッチDNA修復機構の不全によりdGM発生頻度が大幅に上昇することを見出しており、二つの機構が正常に機能することは生殖細胞ゲノム維持に重要であることを明らかにしている。本シンポジウムでは、ヒトやマウスの生殖細胞突然変異研究の現状と、我々の最近の研究成果を紹介し、生殖細胞ゲノム維持機構の理解へ向けての情報を提供したい。

Event date： 2016.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：つくば   Country：Japan  

Event date： 2016.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2016.9

Language：Japanese  

Venue：三島   Country：Japan  

Event date： 2016.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：三島   Country：Japan  

Event date： 2015.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：九州大学   Country：Japan  

Event date： 2015.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：神戸   Country：Japan  

Event date： 2015.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Event date： 2015.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Event date： 2015.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Event date： 2015.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Event date： 2015.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：名古屋   Country：Japan  

Event date： 2015.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名古屋   Country：Japan  

Event date： 2015.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：仙台   Country：Japan  

Event date： 2015.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：仙台   Country：Japan  

Event date： 2015.7 - 2015.8

Language：English   Presentation type：Oral presentation (general)  

Venue：Cairns, Australia   Country：Australia  

Event date： 2015.5

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Kyoto   Country：Japan  

Event date： 2014.12

Language：Japanese  

Venue：東京   Country：Japan  

Event date： 2014.12

Language：Japanese  

Venue：東京   Country：Japan  

Event date： 2014.11

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2014.11

Language：Japanese  

Venue：横浜   Country：Japan  

Event date： 2014.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鹿児島   Country：Japan  

Event date： 2014.9

Language：English  

Venue：横浜   Country：Japan  

Event date： 2014.9

Language：Japanese  

Venue：滋賀県長浜市   Country：Japan  

Event date： 2014.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：滋賀県長浜市   Country：Japan  

Event date： 2014.6

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：名古屋   Country：Japan  

Event date： 2012.12

Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Event date： 2012.11

Venue：静岡   Country：Japan  

8-Oxoguanine repair system contribute to maintain stable phenotype of inbred mouse strain

Event date： 2012.10

Venue：Amalfi   Country：Italy  

Event date： 2012.9

Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Deficiency of 8-oxoguanine repair mechanisms increases spontaneous mutation frequency in mouse germ line and consequently causes hereditary congenital abnormalities

Event date： 2011.12

Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2011.11

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2011.11

Presentation type：Oral presentation (general)  

Venue：神戸   Country：Japan  

A study of radiation-induced oxidative DNA damage and its repair in mouse intestine

Event date： 2011.9

Presentation type：Oral presentation (general)  

Venue：京都大学   Country：Japan  

Event date： 2011.8 - 2011.9

Presentation type：Oral presentation (general)  

Venue：Warsaw, Poland   Country：Poland  

The oxidative stress caused by low LET radiation is considered as a risk factor to induce alteration of genetic information. In DNA, among four bases, guanine is most susceptible to oxidation, and its simple oxidized form is 8-oxoguanine (8-oxoG). 8-OxoG is a potent pre-mutagenic lesion because it can pair with adenine as well as with cytosine during DNA replication.
To investigate the oxidative DNA damage caused by reactive oxygen species as an indirect effect of low LET radiation on various cell type, we examined the intestines of wild-type mice received a whole-body irradiation. Using immuno-histochemical method, we detected 8-oxoG in both nuclear DNA and mitochondrial DNA. At 1hour post irradiation (X-ray, 4 and 10 Gy, 1 Gy/min), we observed only slightly increased 8-oxoG in nuclear DNA of intestinal epithelial cells in both villi (non-proliferative cells) and crypt regions (proliferative cell rich). In contrast to the nuclear signal, a significant increase of mitochondrial 8-oxoG in villous epithelial cells (but not in cryptic cells) was observed.
To clarify the oxygen effect, we analyzed cellular oxygen consumption of intestinal epithelial cells by Hypoxiprobe-1. In the intestine of non-irradiated mice, the villous cells were more hypoxic compared to the cryptic cells, however after radiation, oxygen consumption in villous cells increased. These results suggest that X-ray radiation increases the level of 8-oxoG predominantly in mitochondrial DNA and may lead prolonged oxidative stress caused by mitochondrial dysfunction. We will also present the result of testes. We are in the process of investigation to examine the biological effects of X-ray radiation on intestines and testes using various DNA repair-deficient mice.

Event date： 2010.12

Presentation type：Oral presentation (general)  

Venue：神戸   Country：Japan  

8-oxoguanine increases the frequency of meiotic homologous recombination via DNA strand breaks

Event date： 2010.11

Presentation type：Oral presentation (general)  

Venue：筑波   Country：Japan  

It is well known that reactive oxygen species are generated not only by environmental factors but also by normal cellular metabolisms. We have been focusing on the effect of oxidative DNA damage to genome integrity. Previously we suggested that 8-oxoguanine (8-oxoG) is one of the main causes of base substitution and homologous recombination in the mammalian genome. To elucidate the influence of 8-oxoG on germ-line mutations, we analyzed DNA damage, damage response and resulting homologous recombination using testes derived from Ogg1, Mth1 deficient mice or X-ray irradiated wild-type mice. An increased amount of DNA damage as well as an activation of damage response was observed in the spermatocytes derived from testis of these mice. Moreover, we found an increased frequency of meiotic homologous recombination in Ogg1 or Mth1 deficient mice.

Event date： 2010.10

Presentation type：Oral presentation (general)  

Venue：京都   Country：Japan  

Biological sensitivity to radiation differs among cell and organ types, as well as their state of cell cycle when irradiated. This difference in radiation sensitivity can be attributed to multiple factors, including the amount or kind of DNA damage and mechanisms of damage response and repair.
The effect of DNA exposure to radiation is both direct and indirect. The direct effect is the physical break, single or double, in DNA following ionizing radiation exposure. Free radical species, a product of the interaction between radiation and cellular water, results in many chemical and biological changes, producing an indirect effect. Of the latter, prolonged oxidative stress caused by low LET radiation is a risk factor for the alteration of genetic information. Mutations in somatic cells can result in cancer and other diseases, while those occurred in germ cells could potentially be inherited to offspring, and lead to congenital disorders.
To study the effects of radiation-induced oxidative DNA damage and its repair mechanism, we analyzed the DNA damage response in the testis and intestine of X-ray irradiated mice, including damage status, degree of cell death and cell proliferation. Radiation exposure for 2 days and 7 days at 0.5, 1, 2, and 4Gy revealed a pattern of increased immunoreactivity in gH2AX, 53BP1 and Rad51, as well as a decrease in the number of BrdU positive cells within the testis. The same result was not observed in intestinal samples at those time points. The nuclear content of 8-oxoguanine, an oxidized form of guanine, was also analyzed together with the expression of repair factors in different cell types.

Event date： 2009.12

Presentation type：Oral presentation (general)  

Venue：横浜   Country：Japan  

Event date： 2009.11

Presentation type：Oral presentation (general)  

Venue：静岡   Country：Japan  

Event date： 2009.11

Presentation type：Oral presentation (general)  

Venue：広島   Country：Japan  

Event date： 2009.10

Presentation type：Oral presentation (general)  

Venue：横浜   Country：Japan  

Production and analysis of the Ogg1, Mth1, Mutyh triple knockout mouse strain

Event date： 2009.9

Presentation type：Oral presentation (general)  

Venue：長野   Country：Japan  

The influence of oxidative damaged base on germ-line mutation

Event date： 2009.5 - 2009.6

Presentation type：Oral presentation (general)  

Venue：Wistlar   Country：Canada  

Event date： 2008.12 - 2008.10

Country：Japan  

Event date： 2008.12

Venue：神戸   Country：Japan  

Event date： 2008.12

Venue：神戸   Country：Japan  

Event date： 2008.12 - 2008.5

Presentation type：Symposium, workshop panel (public)  

Venue：神戸   Country：Japan  

Event date： 2008.12

Venue：福岡   Country：Japan  

Event date： 2008.10

Country：Japan  

Event date： 2008.10

Country：Japan  

Event date： 2008.9

Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2008.9

Country：Japan  

Event date： 2008.5

Venue：神戸   Country：Japan  

Language：English   Presentation type：Oral presentation (general)  

Venue：Mishima, Shizuoka   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：慶応大学日吉キャンパス   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Language：Japanese  

Country：Japan  

Event date： 2024.1

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：東京   Country：Japan  

Event date： 2023.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2023.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2023.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：神戸   Country：Japan  

Event date： 2023.11

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2023.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2023.11

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2023.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Event date： 2023.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2022.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：幕張   Country：Japan  

Event date： 2022.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：大阪   Country：Japan  

Event date： 2022.9

Language：Japanese  

Venue：大阪   Country：Japan  

Event date： 2022.9

Language：Japanese  

Venue：大阪   Country：Japan  

Event date： 2021.11

Language：Japanese  

Venue：横須賀   Country：Japan  

Event date： 2019.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台   Country：Japan  

Event date： 2019.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Event date： 2019.12

Language：Japanese  

Country：Japan  

Event date： 2018.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名古屋   Country：Japan  

Event date： 2018.12

Language：Japanese  

Country：Japan  

Event date： 2018.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2018.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2018.11

Language：Japanese  

Country：Japan  

Event date： 2018.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：長崎   Country：Japan  

Event date： 2018.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：長崎   Country：Japan  

Event date： 2018.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：長崎   Country：Japan  

Event date： 2018.11

Language：English   Presentation type：Oral presentation (general)  

Venue：Beijing   Country：China  

Event date： 2018.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：京都   Country：Japan  

Event date： 2018.7

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Yokohama   Country：Japan  

Event date： 2018.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Nagoya   Country：Japan  

Event date： 2017.12

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2017.10

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：ユタ州   Country：United States  

Event date： 2017.10

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Snowbird Resort, Salt Lake City Utah   Country：United States  

Event date： 2017.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大分   Country：Japan  

Event date： 2017.6

Language：Japanese  

Country：Japan  

Event date： 2017.5

Language：Japanese  

Venue：仙台   Country：Japan  

Event date： 2017.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Institute Curie, Paris   Country：France  

Event date： 2016.12

Language：Japanese  

Country：Japan  

Event date： 2016.11 - 2016.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：岡山   Country：Japan  

Event date： 2015.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：名古屋   Country：Japan  

Event date： 2015.8 - 2016.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2014.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：鹿児島   Country：Japan  

Event date： 2014.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：滋賀県長浜市   Country：Japan  

Event date： 2010.12

Presentation type：Oral presentation (general)  

Venue：神戸   Country：Japan  

Analysis of radiation induced DNA damage and its repair in intestine and testis

Event date： 2008.10

Country：Japan  

Event date： 2008.9

Country：Japan  

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：慶応大学日吉キャンパス   Country：Japan  

Language：Japanese  

Country：Japan  

Language：Japanese  

Venue：横浜   Country：Japan  

Language：English  

Venue：Monash University, Melbourne   Country：Australia  

Language：Japanese  

Language：English  

Language：English  

Language：English  

Language：English  

Language：English  

Language：English  

Language：English  

Language：English  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Triplex DNA in human interphase nuclei and its function

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Biological significance of human chromosome bands

Language：Japanese   Publisher：(公財)金原一郎記念医学医療振興財団  

＜文献概要＞スーパーオキシド,過酸化水素,ヒドロキシラジカル,一重項酸素などの活性酸素種(reactive oxygen species;ROS)は,細胞内でのエネルギー産生過程などの内的要因によって,また電離放射線や化学物質への曝露などによる外的要因によって生体内で常に発生している。ROSによってDNAが酸化され,様々な酸化損傷塩基が発生する。DNAの酸化損傷が効率的に修復または除去されないと突然変異や細胞死を引き起こす可能性があり,結果的に体細胞ではがんや老化に伴う変性疾病の原因となり,生殖細胞では遺伝性疾患の発生や不妊や流産などのリスクを増加させると考えられる。本稿では,酸化損傷塩基のなかでも,特に8-オキソグアニンの修復と突然変異の抑制機構について最近の知見と共に紹介する。なお,8-オキソグアニン以外の多数の酸化DNA損傷に関しては,優れた総説があるためそちらを参照されたい。

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：4

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：4

Type：Competition, symposium, etc. 

Number of participants：200

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：2

Type：Competition, symposium, etc. 

Number of participants：1,000

Type：Competition, symposium, etc. 

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：1

Number of peer-reviewed articles in Japanese journals：1

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Number of participants：250

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Number of participants：500

Type：Competition, symposium, etc. 

Number of participants：250

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Number of participants：200

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Audience：Infants,　Schoolchildren,　Junior students,　High school students

Audience：Infants,　Schoolchildren,　Junior students,　High school students

Type：Other

Audience：Infants,　Schoolchildren,　Junior students,　High school students

Type：Seminar, workshop

Audience：Infants,　Schoolchildren,　Junior students,　High school students

Type：Other

Audience：Infants,　Schoolchildren,　Junior students,　High school students

Type：Seminar, workshop